CN111281855B - Rabeprazole enteric-coated tablet and preparation method thereof - Google Patents
Rabeprazole enteric-coated tablet and preparation method thereof Download PDFInfo
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- CN111281855B CN111281855B CN202010207875.4A CN202010207875A CN111281855B CN 111281855 B CN111281855 B CN 111281855B CN 202010207875 A CN202010207875 A CN 202010207875A CN 111281855 B CN111281855 B CN 111281855B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2893—Tablet coating processes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention provides rabeprazole enteric-coated tablets and a preparation method thereof. Granulating, drying and mixing magnesium oxide and other materials such as raw materials, tabletting and coating to obtain enteric-coated tablet, and drying after coating while strictly controlling temperature and water content. Compared with the existing preparation, the invention obviously improves the stability of related substances of the preparation.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a preparation method of rabeprazole enteric-coated tablets.
Technical Field
13 hundred million people in China and 1.2 million patients with intestinal tract diseases (by 2019), wherein the middle-aged and elderly people account for more than 70 percent, the incidence rate of peptic ulcer diseases is 10 percent, the incidence rate of chronic gastritis diseases is 30 percent, and the traditional Chinese medicine is a credible stomach disease kingdom all over the world.
With the acceleration of life rhythm and the change of living structure, the incidence of gastrointestinal diseases is higher and higher. When living is irregular, mental stress, overfatigue, bad mood, massive smoking, surgery, serious burn or bacterial infection, the function of cerebral cortex is disordered, and the nerve of gastric acid secretion can not be well controlled, so as to promote the increase of gastric acid secretion. Improper diet can also lead to increased gastric acid secretion when eating irregularly, long-term alcohol abuse, spicy food, over-sweet, over-salty, over-spicy, over-acid, over-cold and over-hot food; some coarse grains, sweet potatoes, potatoes and the like contain a large amount of starch, sugar, acid and the like, can stimulate the stomach to generate a large amount of gastric acid, and in addition, the indigestible food drinks too much soda water, and the residual sugar is fermented in the gastrointestinal tract, and can also induce pantothenic acid. Gastric acid elevation can lead to chronic gastritis, gastric or duodenal ulcers, and the like.
Currently, acid-inhibiting drugs are divided into two categories: (1) proton Pump Inhibitor (PPI): omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole; (2) tissue H2 receptor inhibitors (H2RA) cimetidine, ranitidine, famotidine, nizatidine, roxatidine, and the like.
Rabeprazole sodium enteric-coated tablets are a new generation of proton pump inhibitors developed by Eisai co., Ltd, and marketed in japan in 1997 for gastric ulcer, duodenal ulcer, stomal ulcer, reflux esophagitis, Zollinger-Ellison syndrome. Can be used for treating gastric ulcer or duodenal ulcer by eradicating helicobacter pylori. The US FDA (10 mg and 20mg specification) was marketed in 1999, the European Union was approved for marketing in 1998 (10 mg and 20mg specification), and the Chinese was approved in 2009 (10 mg and 20mg specification). Rabeprazole has the following structural formula:
rabeprazole bulk drug is unstable to humidity, temperature and light and is unstable at low pH value, higher requirements are put on the production process and environment in the preparation production process, and the problem of stability of related substances of preparation products is urgently needed to be solved. The prior art methods of improving the stability of active ingredients have generally been to add specific compound or compounds to act as inhibitors of the deterioration of the active ingredient; however, the addition of additional components requires both safety considerations and also adjustment of the distribution ratios of the other components, requires considerable research effort, and is not applicable to any active ingredient.
In the production process of the rabeprazole enteric-coated tablet, a series of measures are used, and the stability of the medicament in the storage process is improved through high-temperature magnesium oxide calcination and other measures for controlling moisture in the manufacturing process, so that the stability of the product is better than that of related substances in the existing market.
Disclosure of Invention
The invention aims to overcome the stability problem of the existing rabeprazole enteric-coated tablets in the storage process and provide a preparation method of the rabeprazole enteric-coated tablets, which enables the stability of related substances to be higher.
The preparation method comprises the following steps:
(1) preparing materials:
uniformly mixing rabeprazole, magnesium oxide and auxiliary materials; the magnesium oxide is pretreated before mixing, the pretreatment method comprises the steps of calcining the magnesium oxide at the temperature of 400-700 ℃ for more than 15min, and then cooling the magnesium oxide for later use in the environment with the relative humidity less than or equal to 40%;
(2) wet granulation, drying and total mixing: uniformly mixing materials in the step 1), performing wet granulation by using absolute ethyl alcohol, drying by using a fluidized bed, controlling the moisture of dry granules to be less than or equal to 1.5%, and adding a lubricant for total mixing;
(3) tabletting: the environmental humidity of the tabletting process is controlled to be less than or equal to 50 percent.
(4) Coating and drying:
firstly coating an isolating layer, controlling the temperature of a tablet bed to be 50-60 ℃ after the isolating layer is coated, baking the isolating layer for more than 30min, then coating an enteric-coated layer after the temperature of the tablet bed is cooled to 35 ℃, controlling the temperature of the tablet bed to be 55-60 ℃ after the enteric-coated layer is coated, baking the enteric-coated layer for more than 30min, then cooling to normal temperature, and taking out to obtain the rabeprazole enteric-coated tablet.
In a preferred embodiment of the present invention, the calcination temperature of magnesium oxide is 450-600 deg.C, and the calcination time is 30min or more. More preferably, the calcination time is 30min to 60 min.
Except for the calcining temperature and the calcining time, in the experimental process, if the magnesium oxide calcined by the magnesium oxide is cooled in an open environment, the effect of improving the stability of the active ingredient is not obvious, and if the magnesium oxide is kept cooled in a low humidity environment, the effect of improving the stability of the active ingredient is shown.
As a preferable scheme of the invention, in the step (1), the mass ratio of the rabeprazole to the magnesium oxide is 1:4-1: 6.
As a preferred scheme of the invention, in the step (1), the auxiliary materials comprise a diluent, a disintegrating agent and a lubricant, and the mixture ratio of the components is as follows by mass: 1 part of rabeprazole, 4-6 parts of magnesium oxide, 3-6 parts of diluent, 1-3 parts of disintegrant and 0.05-0.15 part of lubricant.
As a preferable scheme of the invention, the diluent is mannitol or lactose, the disintegrating agent is low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose or carboxymethyl starch sodium, and the lubricant is magnesium stearate.
In a preferable embodiment of the present invention, in the step (2), the lubricant is added in an amount of 0.5 to 2% by mass of the total mixture.
The solid content of the coating solution is 4-8%, the solvent is absolute ethyl alcohol, and the solute is magnesium oxide and ethyl cellulose; the temperature of a sheet bed is controlled to be 30-32 ℃ in the process of coating the isolation layer, the atomization pressure is 0.1-0.2Mpa, the magnesium oxide is pretreated before the coating liquid is prepared, the pretreatment method is that the magnesium oxide is calcined for more than 15min at the temperature of 400-700 ℃, and then the magnesium oxide is cooled for standby application in the environment with the relative humidity less than or equal to 40%.
The solid content concentration of the coating liquid selected in the process of coating the enteric layer is 7-9%, the solvent is 75-90% ethanol solution, and the solute is HPMCP: diacetyl glyceride: titanium dioxide: talc powder: yellow iron oxide;
the atomizing pressure is controlled to be 0.1-0.2Mpa in the process of coating the enteric coating, the temperature of a tablet bed is controlled to be 25-27 ℃, and the humidity is less than or equal to 55 percent.
As a preferable scheme of the invention, the mass ratio of the magnesium oxide to the ethyl cellulose in the coating process is 0.5-2.0: 1; HPMCP: diacetyl glyceride: titanium dioxide: talc powder: the mass ratio of the yellow ferric oxide is 12-10: 1.0-1.4: 0.4-0.6: 0.8-1.2: 0.05-1.00.
Compared with the prior art, the invention has the following optimization:
(1) magnesium oxide has been used as an optional auxiliary material in rabeprazole enteric-coated tablets, and the safety of magnesium oxide has been researched by a large number of clinics and experiments. The invention achieves the aim of improving the stability of rabeprazole by pretreating magnesium oxide, is a method without adding other new components, and has no study and report on the method, the method avoids a great deal of research on the safety of new substances, and the pretreatment research on the magnesium oxide also proves that the invention really improves the stability of related substances of tablets.
(2) In order to improve the stability of active ingredients, the invention further adopts absolute ethyl alcohol for granulation in wet granulation on the basis of magnesium oxide pretreatment, and then controls the moisture of materials and the temperature of related processes through process parameters in the processes of fluidized bed drying, tabletting and enteric coating.
Detailed Description
The preparation process and the implementation effect of the preparation of the present invention will now be further described by the following examples, but the scope of the present invention is not limited to the following examples.
Example 1 screening of stability of magnesium oxide to substances of rabeprazole enteric-coated tablet
The determination method comprises the following steps:
(1) after heating the magnesium oxide for 60min at different temperatures (see table 1), the magnesium oxide is cooled to less than or equal to 30 ℃ in a low-humidity environment (the relative humidity is less than or equal to 40%) for later use.
(2) Respectively adopting 10 parts of magnesium oxide treated at different temperatures in Table 1, adding 2 parts of rabeprazole, 5 parts of mannitol, 2 parts of hydroxypropyl cellulose and 2 parts of low-substituted hydroxypropyl cellulose, uniformly mixing, adding absolute ethyl alcohol to prepare a soft material, sieving by a 24-mesh sieve, pouring into a fluidized bed, drying until the moisture is less than or equal to 1.5%, and drying and finishing by the 24-mesh sieve to obtain dry particles.
(3) And (3) obtaining each dry particle in the step (2), adding 1% of magnesium stearate, tabletting, and breaking the plain tablets at the high temperature of 80 ℃, and detecting related substances at the high temperature of 5 hours by using a USP raw material method. As can be seen from the results in Table 1, the heating temperature of 450 ℃ and 600 ℃ is good.
TABLE 1 stability of materials involved in preparing tablets after heating magnesium oxide at different temperatures
The impurity A and the impurity C have the structural formulas shown as follows, and the impurity A and the impurity C have no activity of rabeprazole sodium and influence the drug effect of the rabeprazole sodium enteric-coated tablets.
Rabeprazole impurity A (molecular weight: 375.45) rabeprazole impurity C (molecular weight: 305.79)
A method for detecting rabeprazole impurity A and impurity C (USP raw material detection method):
(1) mobile phase: solution A: acetonitrile and ammonium acetate;
solution B methanol and ammonium acetate solution (85:15)
Ammonium acetate solution: 5g/L ammonium acetate aqueous solution. (note-if a post-elution interference peak appears in the chromatogram, then filtration through the C18 extraction tray.
(2) Diluent agent: acetonitrile and buffer (20:80)
Buffer solution: water, 0.1N sodium hydroxide solution and 0.1M sodium borate solution (625: 255: 120). The pH was adjusted to 11.3 with 0.1N sodium hydroxide or 0.1M sodium borate as needed.
Solution A: acetonitrile and ammonium acetate solution (5:95) solution B: methanol and ammonium acetate solution (85:15)
(3) Elution procedure:
| Time | mobile phase A | Mobile phase B |
| 0.0 | 100 | 0 |
| 20.0 | 0 | 100 |
| 22.0 | 0 | 100 |
| 22.01 | 100 | 0 |
| 30.0 | 100 | 0 |
(4) A chromatographic column: c18 reverse phase chromatographic column
(5) Adopting buffer solution to prepare appropriate concentrations of impurity A and impurity C as reference solution; and (4) carrying out impurity content statistics by adopting an area normalization method.
Example 2 investigation of the effect of different calcination times of magnesium oxide on the stability of the substances involved in rabeprazole enteric-coated tablet
The determination method comprises the following steps:
(1) calcining magnesium oxide at 450 ℃ for different times, heating for 0min, 15min, 30min and 60min (see table 2), and cooling to less than or equal to 30 ℃ in a low-humidity environment (the relative humidity is less than or equal to 40%).
(2) Respectively adopting 10 parts of magnesium oxide treated by the method in the table 1, adding 2 parts of rabeprazole, 5 parts of mannitol, 2 parts of hydroxypropyl cellulose and 2 parts of low-substituted hydroxypropyl cellulose, uniformly mixing, adding absolute ethyl alcohol to prepare a soft material, sieving by a 24-mesh sieve, pouring into a fluidized bed, drying until the moisture is less than or equal to 1.5%, and performing drying finishing by the 24-mesh sieve to obtain dry particles.
(4) Each of the dry granules obtained in (2) was added with 1% magnesium stearate, tableted, and then disrupted at 80 ℃ at high temperature, and impurities A and C were detected by the high temperature disruption sampling and detection method in example 1. As can be seen from the results in Table 2, the effect is better when the heating time is controlled to be 30-60 min.
TABLE 2 stability of the materials of the tablets prepared with magnesium oxide at different calcination times
Example 3 stability of substances involved in the preparation of rabeprazole tablet intermediates using calcined magnesia, sodium carbonate and calcium phosphate
Measurement method
(1) Preparation:
table 3 table of composition formulations of example 3
| 3-1 | 3-2 | 3-3 | |
| Rabeprazole sodium | 1 part of | 1 part of | 1 part of |
| Mannitol | 6 portions of | 6 portions of | 6 portions of |
| Basic auxiliary material | 10 parts of magnesium oxide | 1 part of sodium carbonate | 10 parts of calcium phosphate |
| Hydroxypropyl cellulose | 2 portions of | 2 portions of | 2 portions of |
| Low-substituted hydroxypropyl cellulose | 3 portions of | 3 portions of | 3 portions of |
| Magnesium stearate | 0.05 to 1 portion | 0.05-1 part | 0.05 to 1 portion |
After heating the magnesium oxide for 60min at different temperatures (see table 1), the magnesium oxide is cooled to less than or equal to 30 ℃ in a low-humidity environment (the relative humidity is less than or equal to 40%) for later use.
According to the composition proportion of 3-1, 3-2 and 3-3, rabeprazole, mannitol, an alkaline auxiliary material, hydroxypropyl cellulose and low-substituted hydroxypropyl cellulose are mixed uniformly, absolute ethyl alcohol is added to prepare a soft material, then the soft material is sieved by a 24-mesh sieve, poured into a fluidized bed and dried until the moisture is less than or equal to 1.5%, and dried and finished by the 24-mesh sieve to obtain dry particles.
(2) To each dry granule, 0.05-1 part of magnesium stearate was added, and after tableting, the plain tablets were put to high temperature 80 ℃ for destruction, and impurities a and C were detected by the high temperature destruction sampling and detection method in example 1. As can be seen from table 4, both impurity a and impurity C of the rabeprazole sodium enteric-coated tablets prepared from calcined magnesia are more stable than sodium carbonate or calcium phosphate.
TABLE 4 comparison of basic auxiliary materials
Example 4 Effect of controlling drying temperature of enteric coating on substance stability of rabeprazole enteric-coated tablet
(1) The calcined magnesium oxide of example 2 was used for 30min and the prepared plain tablets were preheated in a coating pan.
(2) Coating an isolation layer: the solid content of the coating solution is 6 percent, and the coating solution is calculated according to 2 percent of theoretical weight gain of the plain tablets. The solvent is absolute ethyl alcohol, and the solute proportion is magnesium oxide: ethyl cellulose 1: 1. Controlling the temperature of the sheet bed to be 30-32 ℃ and the atomization pressure to be 0.1-0.2 Mpa. After the isolating layer is coated, the temperature of the tablet bed is controlled to be about 60 ℃, the isolating layer sheet is dried for 30min, and after the temperature of the tablet bed is cooled to 35 ℃, the enteric-coated layer is coated.
(3) Coating an enteric layer: the coating solution has a solid content of 9% (calculated by HPMCP) based on the theoretical weight gain of 10% of the tablet. The solvent is 85% ethanol solution. The solute ratio is HPMCP: diacetyl glyceride: titanium dioxide: talc powder: yellow iron oxide 12: 1.2: 0.6: 1.13: 0.07. the preparation method comprises the following steps: weighing HPMCP, uniformly adding the HPMCP into a vortex along a vortex section, adding diacetyl glyceride and water after particles are dissolved, sequentially adding titanium dioxide (which is an ethanol solution prepared by adding anhydrous ethanol to make the solution 80 percent), talcum powder and yellow ferric oxide (which is dispersed by anhydrous alcohol) which are sieved by a 200-mesh sieve after the solution is stirred to be clear and transparent, and stirring for at least 45 minutes. The atomization pressure is 0.1-0.2Mpa, the temperature of the sheet bed is controlled to be 26 +/-1 ℃, and the room humidity is 50-55%.
(4) After the enteric-coated layer is coated, the temperature of the tablet bed is respectively controlled according to the temperature in the table 5, the enteric-coated layer is dried for 1 hour, and the enteric-coated layer is taken out after being cooled to the normal temperature.
(5) And (3) putting each sample obtained in the step (4) at a high temperature of 80 ℃ for destruction, and detecting related substances of 0h, 2h, 5h and 8h by using a USP raw material method with a reference preparation Borite (batch number: 1706094). From the results in Table 5, it can be seen that the bed temperature after coating was 55-60 ℃.
TABLE 5 influence of drying temperature of enteric coating on stability of related substances of rabeprazole enteric-coated tablets
Claims (10)
1. A preparation method of rabeprazole enteric-coated tablets comprises the following steps:
(1) preparing materials:
uniformly mixing rabeprazole, magnesium oxide and auxiliary materials; the magnesium oxide is pretreated before mixing, the pretreatment method comprises the steps of calcining the magnesium oxide at the temperature of 400-700 ℃ for more than 15min, and then cooling the magnesium oxide for later use in the environment with the relative humidity less than or equal to 40%;
(2) wet granulation, drying and total mixing: uniformly mixing materials in the step 1), performing wet granulation by using absolute ethyl alcohol, drying by using a fluidized bed, controlling the moisture of dry granules to be less than or equal to 1.5%, and adding a lubricant for total mixing;
(3) tabletting: the environmental humidity controlled in the tabletting process is less than or equal to 50%;
(4) coating and drying:
firstly coating an isolating layer, controlling the temperature of a tablet bed to be 50-60 ℃ after the isolating layer is coated, baking the isolating layer for more than 30min, then coating an enteric-coated layer after the temperature of the tablet bed is cooled to be below 35 ℃, controlling the temperature of the tablet bed to be 55-60 ℃ after the enteric-coated layer is coated, baking the enteric-coated layer for more than 30min, then cooling to normal temperature, and taking out the rabeprazole enteric-coated tablet.
2. The preparation method according to claim 1, wherein the calcination temperature of the magnesium oxide is 450-600 ℃ and the calcination time is 30min or more.
3. The process according to claim 1 or 2, wherein the magnesium oxide is calcined and then cooled to a temperature of ≦ 30 ℃ for further use.
4. The preparation method according to claim 1, wherein in the step (1), the mass ratio of rabeprazole to magnesium oxide is 1:4-1: 6.
5. The preparation method according to claim 1, wherein in the step (1), the auxiliary materials comprise a diluent, a disintegrant and a lubricant, and the mixture ratio of the components is as follows in parts by mass: 1 part of rabeprazole, 4-6 parts of magnesium oxide, 3-6 parts of diluent, 1-3 parts of disintegrant and 0.05-0.15 part of lubricant.
6. The process according to claim 5, wherein the diluent is mannitol or lactose; the disintegrating agent is low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose or carboxymethyl starch sodium, and the lubricant is magnesium stearate.
7. The method of claim 1, wherein the encapsulating layer process is: the solid content of the coating solution is 4-8%, the solvent is absolute ethyl alcohol, and the solute is magnesium oxide and ethyl cellulose; the temperature of a sheet bed is controlled to be 30-32 ℃ in the process of coating the isolation layer, the atomization pressure is 0.1-0.2Mpa, the magnesium oxide is pretreated before the coating liquid is prepared, the pretreatment method is that the magnesium oxide is calcined for more than 15min at the temperature of 400-700 ℃, and then the magnesium oxide is cooled for standby application in the environment with the relative humidity less than or equal to 40%.
8. The preparation method according to claim 7, wherein the coating solution used in the process of coating the enteric layer has a solid content of 7-9%, the solvent is 75-90% ethanol solution, and the solute is HPMCP: diacetyl glyceride: titanium dioxide: talc powder: yellow iron oxide;
the atomizing pressure is controlled to be 0.1-0.2Mpa in the process of coating the enteric coating, the temperature of a tablet bed is controlled to be 25-27 ℃, and the humidity is less than or equal to 55 percent.
9. The preparation method according to claim 8, wherein the mass ratio of the magnesium oxide to the ethyl cellulose is 0.5-2.0: 1; HPMCP: diacetyl glyceride: titanium dioxide: talc powder: the mass ratio of the yellow ferric oxide is 12-10: 1.0-1.4: 0.4-0.6: 0.8-1.2: 0.05-1.00.
10. Rabeprazole enteric-coated tablets prepared by the method of any one of claims 1 to 9.
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